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COMMD1 upregulation is involved in copper efflux from ischemic hearts
Authors:Chen Li  Tao Wang  Ying Xiao  Kui Li  Xia Meng  Y James Kang
Institution:1.Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China; 2.Memphis Institute of Regenerative Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Abstract:Copper depletion is associated with myocardial ischemic infarction, in which copper metabolism MURR domain 1 (COMMD1) is increased. The present study was undertaken to test the hypothesis that the elevated COMMD1 is responsible for copper loss from the ischemic myocardium, thus worsening myocardial ischemic injury. Mice (C57BL/6J) were subjected to left anterior descending coronary artery permanent ligation to induce myocardial ischemic infarction. In the ischemic myocardium, copper reduction was associated with a significant increase in the protein level of COMMD1. A tamoxifen-inducible, cardiomyocyte -specific Commd1 knockout mouse (C57BL/6J) model (COMMD1CMC▲/▲) was generated using the Cre-LoxP recombination system. COMMD1CMC▲/▲ and wild-type littermates were subjected to the same permanent ligation of left anterior descending coronary artery. At the 7th day after ischemic insult, COMMD1 deficiency suppressed copper loss in the heart, along with preservation of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 expression and the integrity of the vascular system in the ischemic myocardium. Corresponding to this change, infarct size of ischemic heart was reduced and myocardial contractile function was well preserved in COMMD1CMC▲/▲ mice. These results thus demonstrate that upregulation of COMMD1 is at least partially responsible for copper efflux from the ischemic heart. Cardiomyocyte-specific deletion of COMMD1 helps preserve the availability of copper for angiogenesis, thus suppressing myocardial ischemic dysfunction.
Keywords:Myocardial ischemia  copper efflux  COMMD1  cardiac function
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